spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 21 April 2004
doi: 10.1242/dev.01125

Development 131, 2257-2268 (2004)
Published by The Company of Biologists 2004
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.01125v1
131/10/2257    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andl, T.
Right arrow Articles by Millar, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andl, T.
Right arrow Articles by Millar, S. E.

Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development

Thomas Andl1, Kyung Ahn3, Alladin Kairo1, Emily Y. Chu1, Lara Wine-Lee3, Seshamma T. Reddy1, Nirvana J. Croft1, Judith A. Cebra-Thomas1, Daniel Metzger4, Pierre Chambon4, Karen M. Lyons5, Yuji Mishina6, John T. Seykora1, E. Bryan Crenshaw, III3 and Sarah E. Millar1,2,*

1 Department of Dermatology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
2 Department of Cell and Developmental Biology, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
3 Center for Childhood Communication, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
4 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, BP 163, 67404 Illkirch Cedex, France
5 Departments of Molecular, Cell and Developmental Biology, Orthopaedic Surgery, and Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
6 Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

* Author for correspondence (e-mail: millars{at}mail.med.upenn.edu)

Accepted 5 February 2004

Bone morphogenetic protein (BMP) signaling is thought to perform multiple functions in the regulation of skin appendage morphogenesis and the postnatal growth of hair follicles. However, definitive genetic evidence for these roles has been lacking. Here, we show that Cre-mediated mutation of the gene encoding BMP receptor 1A in the surface epithelium and its derivatives causes arrest of tooth morphogenesis and lack of external hair. The hair shaft and hair follicle inner root sheath (IRS) fail to differentiate, and expression of the known transcriptional regulators of follicular differentiation Msx1, Msx2, Foxn1 and Gata3 is markedly downregulated or absent in mutant follicles. Lef1 expression is maintained, but nuclear ß-catenin is absent from the epithelium of severely affected mutant follicles, indicating that activation of the WNT pathway lies downstream of BMPR1A signaling in postnatal follicles. Mutant hair follicles fail to undergo programmed regression, and instead continue to proliferate, producing follicular cysts and matricomas. These results provide definitive genetic evidence that epithelial Bmpr1a is required for completion of tooth morphogenesis, and regulates terminal differentiation and proliferation in postnatal hair follicles.

Key words: Hair follicle, Skin, Tooth, BMP, BMPR1A, BMPR1B, ß-catenin, Gata3, Msx, Foxn1






© The Company of Biologists Ltd 2004